Stacey N H
Toxicol Appl Pharmacol. 1986 Feb;82(2):224-32. doi: 10.1016/0041-008x(86)90197-3.
The biochemical mechanism involved in cadmium-induced cellular injury remains to be elucidated. Various theories have been proposed to account for this action, one of which is an interaction with reduced sulfhydryl (SH) groups of membranes. The ability of a known SH group reducing agent, dithiothreitol (DTT), to interact with cadmium-induced damage to isolated hepatocytes was investigated. Cadmium chloride produced a cytotoxic response similar to that previously demonstrated. When added just prior to cadmium chloride, DTT was found to protect against the metal-induced injury. If the cells were first exposed to cadmium for 15 min before DTT was added, it was found that the cells could be rescued from the ensuing expression of toxicity due to cadmium. This result was regardless of the fact that by 15 min the cells had accumulated a quantity of cadmium that was associated with cell injury. Furthermore, DTT did not exert its action by decreasing the amount of cadmium accumulation by the cells. Under some experimental conditions, an increased cadmium uptake in the presence of DTT was observed. While it is not clear as to whether the chelating or thiol reductive properties of DTT are of prime importance in the demonstrated protection, the data show that toxicity is not due to a simple, single irreversible interaction between cadmium and membrane SH groups.
镉诱导细胞损伤所涉及的生化机制仍有待阐明。人们提出了各种理论来解释这种作用，其中之一是与膜的还原巯基（SH）基团相互作用。研究了一种已知的SH基团还原剂二硫苏糖醇（DTT）与镉诱导的离体肝细胞损伤相互作用的能力。氯化镉产生了与先前证明的类似的细胞毒性反应。当在氯化镉之前加入DTT时，发现它能保护细胞免受金属诱导的损伤。如果在加入DTT之前先将细胞暴露于镉15分钟，发现细胞可以从随后因镉引起的毒性表达中被挽救。无论事实上到15分钟时细胞已经积累了一定量与细胞损伤相关的镉，结果都是如此。此外，DTT并不是通过减少细胞对镉的积累量来发挥其作用的。在某些实验条件下，观察到在DTT存在下镉的摄取增加。虽然尚不清楚DTT的螯合或硫醇还原特性在所示的保护作用中是否至关重要，但数据表明毒性并非由于镉与膜SH基团之间简单的单一不可逆相互作用所致。
